GPs' decisions on drug treatment for patients with high cholesterol values: A think-aloud study

BACKGROUND: The purpose was to examine how General Practitioners (GPs) use clinical information and rules from guidelines in their decisions on drug treatment for high cholesterol values. METHODS: Twenty GPs were presented with six case vignettes and were instructed to think aloud while successively more information about a case was presented, and finally to decide if a drug should be prescribed or not. The statements were coded for the clinical information to which they referred and for favouring or not favouring prescription. RESULTS: The evaluation of clinical information was compatible with decision-making as a search for reasons or arguments. Lifestyle-related information like smoking and overweight seemed to be evaluated from different perspectives. A patient's smoking favoured treatment for some GPs and disfavoured treatment for others. CONCLUSIONS: The method promised to be useful for understanding why doctors differ in their decisions on the same patient descriptions and why rules from the guidelines are not followed strictly

BE-SAFE: Bedside Sonography for Assessment of the Fetus in Emergencies: Educational Intervention for Late-pregnancy Obstetric Ultrasound

Introduction: Late obstetric emergencies are time critical presentations in the emergency department. Evaluation to ensure the safety of mother and child includes rapid assessment of fetal viability, fetal heart rate (FHR), fetal lie, and estimated gestational age (EGA). Point-of-care (POC) obstetric ultrasound (OBUS) offers the advantage of being able to provide all these measurements. We studied the impact of POC OBUS training on emergency physician (EP) confidence, knowledge, and OBUS skill performance on a live model. Methods: This is a prospective observational study evaluating an educational intervention we designed, called the BE-SAFE curriculum (BEdside Sonography for the Assessment of the Fetus in Emergencies). Subjects were a convenience sample of EP attendings (N=17) and residents (N=14). Prior to the educational intervention, participants completed a self-assessment survey on their confidence regarding OBUS, and took a pre-test to assess their baseline knowledge of OBUS. They then completed a 3-hour training session consisting of didactic and hands-on education in OBUS. After training, each subject’s time and accuracy of performance of FHR, EGA, and fetal lie was recorded. Post-intervention knowledge tests and confidence surveys were administered. Results were compared with non-parametric t-tests. Results: Pre- and post-test knowledge assessment scores for previously untrained EPs improved from 65.7% [SD=20.8] to 90% [SD=8.2] (p<0.0007). Self-confidence on a scale of 1–6 improved significantly for identification of FHR, fetal lie, and EGA. After training, the average times for completion of OBUS critical skills were as follows: cardiac activity (9s), FHR (68.6s), fetal lie (28.1s), and EGA (158.1 sec). EGA estimates averaged 28w0d (25w0d-30w6d) for the model’s true gestational age of 27w0d. Conclusion: After a focused POC OBUS training intervention, the BE-SAFE educational intervention, EPs can accurately and rapidly use ultrasound to determine FHR, fetal lie, and estimate gestational age in mid-late pregnancy

NMR Structure and Dynamics of TonB Investigated by Scar-Less Segmental Isotopic Labeling Using a Salt-Inducible Split Intein

The growing understanding of partially unfolded proteins increasingly points to their biological relevance in allosteric regulation, complex formation, and protein design. However, the structural characterization of disordered proteins remains challenging. NMR methods can access both the dynamics and structures of such proteins, yet suffering from a high degeneracy of NMR signals. Here, we overcame this bottleneck utilizing a salt-inducible split intein to produce segmentally isotope-labeled samples with the native sequence, including the ligation junction. With this technique, we investigated the NMR structure and conformational dynamics of TonB from Helicobacter pylori in the presence of a proline-rich low complexity region. Spin relaxation experiments suggest that the several nano-second time scale dynamics of the C-terminal domain (CTD) is almost independent of the faster pico-to-nanosecond dynamics of the low complexity central region (LCCR). Our results demonstrate the utility of segmental isotopic labeling for proteins with heterogenous dynamics such as TonB and could advance NMR studies of other partially unfolded proteins.Peer reviewe

An Image-Analysis-Based Method for the Prediction of Recombinant Protein Fiber Tensile Strength

Silk fibers derived from the cocoon of silk moths and the wide range of silks produced by spiders exhibit an array of features, such as extraordinary tensile strength, elasticity, and adhesive properties. The functional features and mechanical properties can be derived from the structural composition and organization of the silk fibers. Artificial recombinant protein fibers based on engineered spider silk proteins have been successfully made previously and represent a promising way towards the large-scale production of fibers with predesigned features. However, for the production and use of protein fibers, there is a need for reliable objective quality control procedures that could be automated and that do not destroy the fibers in the process. Furthermore, there is still a lack of understanding the specifics of how the structural composition and organization relate to the ultimate function of silk-like fibers. In this study, we develop a new method for the categorization of protein fibers that enabled a highly accurate prediction of fiber tensile strength. Based on the use of a common light microscope equipped with polarizers together with image analysis for the precise determination of fiber morphology and optical properties, this represents an easy-to-use, objective non-destructive quality control process for protein fiber manufacturing and provides further insights into the link between the supramolecular organization and mechanical functionality of protein fibers

INTEROP deliverable DTG 6.2 : Method repository

This deliverable presents the INTEROP method chunks repository (MCR), its architecture and provided services. It includes the definition of a reusable method chunk, its structure, illustrated with examples of method chunks stored in the repository and guidelines for method chunks definition and characterisation covering tasks TG6.2 and TG6.3 of the work plan of the task group. The main result is the definition of the structure of the method chunk repository emphasizing the link to interoperability. Interoperability is a first-class concept in the structure of the method chunk repository. It not only characterizes method chunks, i.e. procedures to solve interoperability problems, but also interoperability cases, i.e. the presentation of actual problems involving interoperability issues. TG 6 has produced three MCR prototypes. Two experiments were undertaken using the Metis system and one using ConceptBase. The task group attended a two-day intense workshop on Metis. As a result, two experiments with Metis as platform for the method chunk repository are under way and reported in this deliverable. One is realizing the structure of the MCR as specified in this report. The other is an alternative approach that serves as a benchmark and is reported in the appendix. The ConceptBase prototype utilizes the metamodel presented in this deliverable. We have analysed three cases involving various aspects of interoperability. One case is about establishing a broker platform for insurance agents, the second about linking the information systems in the public utility sector, and the third case is establishing the relation of the ATHENA Model-Driven Interoperability Framework to the goals of the MCR. The results of the TG6 have been published at the ISD conference 2006 and the ER conference 2006. Copies of the papers are included in the appendix. The report of the example session with the method chunk repository has been shifted towards deliverable TG6.3 (Tutorial of the MCR). This is the more logical place. We want to emphasize that TG6 was not only busy in drafting concepts, exploring the state of the art, and analyzing cases. We are actually experimenting with a prototype and consider this a valuable contribution to the network. As soon as the prototype is stable, knowledge about interoperability solutions can be coded in this repository and can guide designers of interoperable systems by experience knowledge

Anti-biofilm action of nitric oxide-releasing alkyl-modified poly(amidoamine) dendrimers against Streptococcus mutans

The effect of nitric oxide (NO)-releasing dendrimer hydrophobicity on Streptococcus mutans killing and biofilm disruption was examined at pH 7.4 and 6.4, the latter relevant to dental caries. Generation 1 (G1) poly(amidoamine) (PAMAM) dendrimers were modified with alkyl epoxides to generate propyl-, butyl-, hexyl-, octyl-, and dodecyl-functionalized dendrimers. The resulting secondary amines were reacted with NO to form N-diazeniumdiolate NO donor-modified dendrimer scaffolds (total NO ∼1μmol/mg). The bactericidal action of the NO-releasing dendrimers against both planktonic and biofilm-based S. mutans proved greatest with increasing alkyl chain length and at lower pH. Improved bactericidal efficacy at pH 6.4 was attributed to increased scaffold surface charge that enhanced dendrimer-bacteria association and ensuing membrane damage. For shorter alkyl chain (i.e., propyl and butyl) dendrimer modifications, increased antibacterial action at pH 6.4 was due to faster NO-release kinetics from proton-labile N-diazeniumdiolate NO donors. Octyl- and dodecyl-modified PAMAM dendrimers proved most effective for eradicating S. mutans biofilms with NO release mitigating dendrimer scaffold cytotoxicity. We report the antibacterial and anti-biofilm efficacy of dual-action nitric oxide (NO)-releasing dendrimers against S. mutans, an etiological agent in dental caries. This work was undertaken to enhance the anti-biofilm action of these scaffolds by employing various alkyl chain modifications. Furthermore, we evaluated the ability of NO to eradicate cariogenic biofilms. We found that at the lower pH associated with dental caries (pH ∼6.4), NO has a more pronounced antibacterial effect for alkyl modifications less capable of biofilm penetration and membrane disruption. Of greatest significance, we introduce dendrimers as a new macromolecular antibacterial agent against the cariogenic bacteria S. mutans

Progression of Carotid Artery Intima-Media Thickness During 12 Years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

OBJECTIVE This study investigated the long-term effects of intensive diabetic treatment on the progression of atherosclerosis, measured as common carotid artery intima-media thickness (IMT). RESEARCH DESIGN AND METHODS A total of 1,116 participants (52% men) in the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, a long-term follow-up of the Diabetes Control and Complications Trial (DCCT), had carotid IMT measurements at EDIC years 1, 6, and 12. Mean age was 46 years, with diabetes duration of 24.5 years at EDIC year 12. Differences in IMT progression between DCCT intensive and conventional treatment groups were examined, controlling for clinical characteristics, IMT reader, and imaging device. RESULTS Common carotid IMT progression from EDIC years 1 to 6 was 0.019 mm less in intensive than in conventional (P < 0.0001), and from years 1 to 12 was 0.014 mm less (P = 0.048); but change from years 6 to 12 was similar (intensive − conventional = 0.005 mm, P = 0.379). Mean A1C levels during DCCT and DCCT/EDIC were strongly associated with progression of IMT, explaining most of the differences in IMT progression between DCCT treatment groups. Albuminuria, older age, male sex, smoking, and higher systolic blood pressure were significant predictors of IMT progression. CONCLUSIONS Intensive treatment slowed IMT progression for 6 years after the end of DCCT but did not affect IMT progression thereafter (6–12 years). A beneficial effect of prior intensive treatment was still evident 13 years after DCCT ended. These differences were attenuated but not negated after adjusting for blood pressure. These results support the early initiation and continued maintenance of intensive diabetes management in type 1 diabetes to retard atherosclerosis

Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients

AIMS/INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN. MATERIALS AND METHODS: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R-R intervals (SDNN) and the root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG-derived CAN and CARTs-defined CAN. RESULTS: Participants with CARTs-defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P \u3c 0.001). The optimal cut-off points of ECG-derived CAN were \u3c17.13 and \u3c24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30-0.51) for the optimal cut-off point, showing fair agreement with CARTs-defined CAN. Combining SDNN and rMSSD optimal cut-off points does not provide additional predictive power for CAN. CONCLUSIONS: These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care

Nickel: A very fast diffuser in silicon

Nickel is increasingly used in both IC and photovoltaic device fabrication, yet it has the potential to create highly recombination-active precipitates in silicon. For nearly three decades, the accepted nickel diffusivity in silicon has been DNi(T)=2.3×10exp−3 exp(−0.47 eV/kBT) cm2/s, a surprisingly low value given reports of rapid nickel diffusion in industrial applications. In this paper, we employ modern experimental methods to measure the higher nickel diffusivity DNi(T)=(1.69±0.74)×10exp−4 exp(−0.15±0.04 eV/kBT)  cm2/s. The measured activation energy is close to that predicted by first-principles theory using the nudged-elastic-band method. Our measured diffusivity of nickel is higher than previously published values at temperatures below 1150 °C, and orders of magnitude higher when extrapolated to room temperature.Peer reviewe